We have used synthetic oligonucleotide probes to screen a human melanoma cDNA library. Probes containing sequences similar to those contained in metastasis associated metalloproteinases were used to screen this library. Screening yielded several cDNA clones. Two of these clones have been fully sequenced. The first clone, referred to as C1114.12, contains a 1.7 kB insert. The sequencing of this clone revealed that it contained a novel sequence with a single open reading frame encoding for a unique peptide sequence. Primer extension data are consistent with this clone representing a full-length message. Northern blot analysis suggests that the message size is on the order of 1.9-2.0 kB and that this is a transcript of relatively low abundance. Northern blot analysis also revealed that this message was more abundant in normal mucosal tissue when compared with the transcript levels seen in colon tumors. This suggests that possibly the C1114.12 transcript levels are down regulated in tumor cells. This possibility is being explored further. The second clone is referred to as pM5. This clone contained a 4086 bp insert which contained a single open reading frame which encoded a polypeptide of 1144 amino acid residues. Computerized homology searches revealed no homology with any known sequences both at the protein and at the nucleotide level. This suggests that pM5 is a unique gene product. Specific hydrophilic domains from the pM5 protein sequences have been selected for the generation of antipeptide antibodies. These will be used to determine the subcellular localization of the pM5 gene product and to determine the tissue localization using immunohistochemical techniques.